Brain tumor revealed by atrial sinus block

Bradycardia is rare in children and may be asymptomatic or cause fatigue or discomfort leading to syncope. It may be a warning sign of underlying pathology. A check-up for a cardiac or extra-cardiac organic cause should be performed. We report the case of an 8-year-old child admitted to the emergency room for bradycardia with a sino-atrial block that caused syncope. The assessment has objectified a brain tumor. We will discuss the different mechanisms that can explain the occurrence of bradycardia during a brain tumor, and the specificities of the management.     

Association between sex hormones and migraine in young Saudi females

Objectives:To assess the sex hormone levels in young Saudi female migraineurs during a migraine attack and during pain-free periods and compare them with control subjects.Methods:A case-control study involving 14 Saudi female migraineurs and 21 control subjects was conducted between December 2019 and March 2020. Demographic and disease history data were collected through participant interviews. Blood samples were drawn during the migraine attack and pain-free periods.Results:Follicular (30.00±19.60; p<0.001) and luteal (39.79±11.45; p=0.037) estrogen levels were significantly higher in patients with non-menstrual related migraine (NMM), while luteal testosterone levels (1.10±0.31; p=0.023) were significantly higher in patients with menstrually related migraine (MM). Body mass index (BMI) was higher in patients with NMM (25.77±6.53; p=0.013), and it was found to be associated with follicular estrogen (p=0.016), progesterone (p=0.018), and pain intensity (p=0.042). Luteal estrogen level was significantly lower (13.96±7.88; p=0.036) in patients with luteal onset of attack.Conclusion:High estrogen levels were found to mediate NMM, their effect being more pronounced with increase in BMI; whereas low luteal estrogen levels mediated MM. Young females with MM might have high luteal testosterone levels, and a compensatory protective role could be surmised accordingly.     

In silico identification of potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations

In the present era, there are many efforts trying to face the emerging and successive waves of the COVID-19 pandemic. This has led to considering new and unusual targets for SARS CoV-2. 2′-O-Methyltransferase (nsp16) is a key and attractive target in the SARS CoV-2 life cycle since it is responsible for the viral RNA protection via a cap formation process. In this study, we propose a new potential inhibitor for SARS COV-2 2′-O-methyltransferase (nsp16). A fragment library was screened against the co-crystal structure of the SARS COV-2 2′-O-methyltransferase complexed with Sinefungin (nsp16 – PDB ID: 6WKQ), and consequently the best proposed fragments were linked via a de novo approach to build molecule AP-20. Molecule AP-20 displayed a superior docking score to Sinefungin and reproduced the key interactions in the binding site of 2′-O-methyltransferase. Three molecular dynamic simulations of the 2′-O-methyltransferase apo structure and its complexed forms with AP-20 and Sinefungin were performed for 150 nano-seconds to provide insights on the dynamic nature of such setups and to assess the stability of the proposed AP-20/enzyme complex. AP-20/enzyme complex demonstrated better stability for the ligand–enzyme complex compared to Sinefungin in a respective setup. Furthermore, MM-PBSA binding free energy calculations showed a better profile for AP-20/enzyme complex compared to Sinefungin/enzyme complex emphasizing the potential inhibitory effect of AP-20 on SARS COV-2 2′-O-methyltransferase. We endorse our designed molecule AP-20 to be further explored via experimental evaluations to confront the spread of the emerging COVID-19. Also, in silico ADME profiling has ascribed to AP-20 an excellent safety and metabolic stability profile.

The identification of AP-20 as a potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations.     

Clinicopathological evaluation of the donor area following autologous suction blister epithelial grafting vs Thiersch grafting in vitiligo patients: A preliminary study

Surgical vitiligo treatment is suggested for recalcitrant small stable lesions. One of the limitations of this approach is the presence of large lesions. The donor site should be designed to be hidden without previous or present lesions; this limits donor sites. Aim of the study was to clinically and histopathologically evaluate donor areas 3 months and 1 year after Thiersch grafting (TG) and suction blister epithelial grafting (SBEG). Forty patients with stable vitiligo were equally divided into two groups before TG and SBEG. In each patient, the donor site was clinically and histopathologically evaluated after 3 months and 1 year. After 3 months in Group I, hyperpigmentation, mixed pigmentation with atrophic scarring, hyperpigmentation with hypertrophic scarring, erythema, and tough skin were detected in 10%, 50%, 10%, 10%, and 20% of cases, respectively. The condition improved with time leaving, leaving tough skin in all cases after 1 year. In Group II, hyperpigmentation was observed in all patients after 3 months and disappeared completely after 1 year. Histologically, biopsies taken 3 months after TG, showed increased basal pigmentation with dermal changes mimicking scar tissue in 92.5% of cases. Collagen homogenization of and fragmented elastic tissue were reported in all cases. Biopsies showed the same features after 1 year. In the SBEG group, biopsies revealed only basal hyperpigmentation that disappeared after 1 year in all patients. We concluded that SBEG is a scarless operation and regrafting from the same area can be performed. This is in contrast to TG, which is considered a scarring operation, and wherein the donor site cannot be reused for grafting.     

Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: in vitro and in vivo assessment

Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. Ex vivo transcorneal permeation was significantly enhanced for CS coated formulation. In vitro cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.     

Gene expression profile of esophageal cancer in North East India by cDNA microarray analysis

AIM: To identify alterations in genes and molecular functional pathways in esophageal cancer in a high incidence region of India where there is a widespread use of tobacco and betel quid with fermented areca nuts. METHODS: Total RNA was isolated from tumor and matched normal tissue of 16 patients with esophageal squamous cell carcinoma. Pooled tumor tissue RNA was labeled with Cy3-dUTP and pooled normal tissue RNA was labeled with Cy5-dUTP by direct labeling method. The labeled probes were hybridized with human 10K cDNA chip and expression profiles were analyzed by Genespring GX V 7.3 (Silicon Genetics). RESULTS: Nine hundred twenty three genes were differentially expressed. Of these, 611 genes were upregulated and 312 genes were downregulated. Using stringent criteria (P ≤ 0.05 and ≥ 1.5 fold change), 127 differentially expressed genes (87 upregulated and 40 downregulated) were identified in tumor tissue. On the basis of Gene Ontology, four different molecular functional pathways (MAPK pathway, G-protein coupled receptor family, ion transport activity, and serine or threonine kinase activity) were most significantly upregulated and six different molecular functional pathways (structural constituent of ribosome, endopeptidase inhibitor activity, structural constituent of cytoskeleton, antioxidant activity, acyl group transferase activity, eukaryotic translation elongation factor activity) were most significantly downregulated. CONCLUSION: Several genes that showed alterations in our study have also been reported from a high incidence area of esophageal cancer in China. This indicates that molecular profiles of esophageal cancer in these two different geographic locations are highly consistent.     

Genetic polymorphism of glutathione S-transferases M1 and T1 in Egyptian patients with bilharzial bladder cancer

ObjectiveTo assess the influence of glutathione S-transferases M1 and T1 (GSTM1 and T1) genotype on the risk of bladder cancer in patients with urinary bilharziasis.Materials and methodsThis study was designed as a case-control study that involved 60 individuals who were enrolled into 3 equal groups. The first one included patients with bilharzial bladder cancer, the second one had those with nonmalignant urinary bilharziasis, and the last one was the control group. All of the participants were adult males, nonsmokers, and with matched ages. All of them underwent an assessment of the serum level of the total GST concentration and the polymerase chain reaction (PCR) was used for determination of the GSTM1 and T1 genotypes.ResultsThe lower most GST enzyme concentration was reported in patients with bilharzial bladder cancer (26 ± 4.4 ng/ml) with significant difference between it and that of the second group (36.8 ± 4.1 ng/ml, P < 0.05) and that of the controls (40.4 ± 4 ng/ml, P < 0.005). The PCR results have demonstrated that the frequency of combined GSTM1 and T1 genes deletion (M1–ve T1–ve) was significantly higher in cases of bladder cancer (40%) than those of the controls (5%, P < 0.005) and those of the second group (10%, P < 0.05). The unconditional logistic regression test revealed that patients with urinary bilharziasis and combined GSTM1 and T1 genes deletion are at a significant risk for malignant transformation (OR = 6.3, P < 0.05).ConclusionsPatients with urinary bilharziasis and GSTM1–ve and T1–ve genes might be at increased risk of bladder cancer. However, larger studies are needed for confirmation of these results.     

The status of serum vitamin D in patients attending a general rheumatology clinic in the UK

Vitamin D deficiency may be involved in the pathogenesis of several inflammatory conditions. This study aimed to determine the status of vitamin D in the rheumatology patients who were diagnosed with different rheumatic, inflammatory and non-inflammatory diseases. In this cross-sectional observational study, we reviewed the levels of serum vitamin D in patients who attended the general rheumatology clinics for the first time between May 2012 and October 2012. A total of 61 patients were included in this study. Twenty-five patients (41 %) had vitamin D insufficiency and two patients (3.3 %) were vitamin D deficient. Sixteen patients had an inflammatory condition and vitamin D was low in five patients (31 %). Among the 45 patients who had a non-inflammatory rheumatic condition, 20 patients (44 %) had low vitamin D. There was no significant statistical difference (P = 0.3) in the incidence of low vitamin D between the two groups. We found no significant correlation either between CRP and vitamin D (r = ?0.02 (95 % confidence interval ?0.28 to 0.23), P = 0.8). In this limited study, which was undertaken in the summer months, we concluded that there was no significant difference in vitamin D status between patients with inflammatory and non-inflammatory rheumatic conditions.     

Cerebral Cavernous Malformations and Pregnancy: Hemorrhage Risk and Influence on Obstetrical Management

BACKGROUND:: Cerebral cavernous malformations are brain vascular malformations associated with intracranial hemorrhage. It is unclear whether pregnancy is a risk factor for hemorrhage, yet there is speculation that it may be. OBJECTIVE:: To compare the risk of clinically significant hemorrhage during pregnancy and nonpregnancy. METHODS:: A total of 186 patients from the University of Toronto Vascular Malformations Study Group were enrolled. The obstetrical history of each patient was collected and matched to their neurological history from the records of the study group. All hemorrhagic events occurring during childbearing years were associated with either a defined pregnancy risk period or nonpregnancy period. Patients were also asked to recall advice that they received from health care professionals regarding risk of hemorrhage in pregnancy. RESULTS:: Among our patient population there were 349 pregnancies (283 live births) and 49 hemorrhages during childbearing years, 3 of which were during pregnancy but none during delivery or within 6 weeks post partum. The hemorrhage rate for pregnant women was 1.15% (95% confidence interval: 0.23-3.35) per person-year and 1.01% (95% confidence interval: 0.75-1.36) per person-year for nonpregnant women. Relative risk of pregnancy was 1.13 (95% confidence interval: 0.34-3.75) (P = .84). Neurosurgeons and obstetricians were the source of most hemorrhage risk advice. The majority of neurosurgeons suggested that the risk was unchanged, but the obstetricians were divided. Four patients never conceived, and 2 others began contraception because of the advice that they received. CONCLUSION:: The risk of intracranial hemorrhage from cerebral cavernous malformations is likely not changed during pregnancy, delivery, or post partum. ABBREVIATIONS:: CCM, cerebral cavernous malformationCI, confidence interval.